SEMINAR ON METABOLISM OF CARBOHYDRATES By Dr.

Kshitij Chaurasia CONTENTS Definition Metabolism Free Energy Carbohydrates Classification Glycolysis Krebs cycle Electron Transport Chain Symmary of ATP production Lactose fermentation Metabolism of Lactic acid Coris cycle Glycogenesis and Glycogenolysis Lipolysis and Lipogenesis Protein metabolism Metabolic disorders

Definitions:
Catabolism = the breakdown of complex substances.

Anabolism = the synthesis of complex substances from simpler ones.

Metabolism
Metabolism = Anabolism + Catabolism EXAMPLE Photosynthesis requires Respiration Respiration requires Photosynthesis

 Energy Production = Energy Consumption

Free Energy Changes in Metabolism

Overall G is negative (-) for catabolic processes example: AB DCDE higher energy lower compound G1 energy compound G2

Carbohydrates

 A carbohydrate is an organic compound with Aldehyde group attached to carbon

chain with hydroxyl groups

General formula Cn(H2O)n Synonym of saccharide

Main source of energy for body Complex carbohydrates (starches) are found in bread, cereal, flour, pasta, nuts, and potatoes Simple carbohydrates (sugars) are found in soft drinks, candy, fruit, and ice cream Major pathways of Carbohydrate metabolism begin or end with glucose Glucose is the molecule ultimately used by body cells to make ATP Neurons and RBCs rely almost entirely upon glucose to supply their energy needs The minimum amount of carbohydrates needed to maintain adequate blood glucose levels is 100 grams per day Excess glucose is converted to glycogen or fat and stored.

Classification of carbohydrates
Monosaccharides Glucose Glactose Fructose Ribose Glyceraldehyde Disaccharides Sucrose Maltose Lactose Polysaccharides Starch Glycogen Cellulose

Stages of Metabolism

Digestion of Carbohydrates
Monosaccharides Do not need hydrolysis before absorption Very little (if any) in most feeds Di- and poly-saccharides Relatively large molecules Must be hydrolyzed prior to absorption Hydrolyzed to monosaccharides Only monosaccharides can be absorbed

Carbohydrate Digestion
Mouth
Salivary amylase breaks starches down to maltose. Plays only a small role in breakdown because of the short time food is in the

mouth Ruminants do not have this enzyme

Digestion in Small Intestine

Pancreas Pancreatic amylase hydrolyzes alpha 1-4 linkages Produces monosaccharides, disaccharides and polysaccharides Major importance in hydrolyzing starch and glycogen to maltose Polysaccharides
AMYLAS

Disaccharides

Digestion in Small Intestine

Digestion mediated by enzymes synthesized by cells lining the small intestine (brush

border)

Brushbord

Disaccharides
Exception is -1,4 bonds in cellulose

Monosaccharides

Sucrose Maltose Lactose

sucrase maltase lactase

Glucose + Fructose Glucose + Glucose Glucose + Glactose

Overview Carbohydrate Digestion

Carbohydrate Metabolism
Since all carbohydrates are transformed into glucose, it is essentially glucose metabolism Oxidation of glucose is shown by the overall reaction: C6H12O6 + 6O2 6H2O + 6CO2 + 36 ATP + heat Glucose is catabolized in three pathways Glycolysis Krebs cycle The electron transport chain and oxidative phosphorylation

Cellular respiration
Glycolysis: cytosol; degrades glucose into pyruvate Krebs Cycle: mitochondrial matrix; pyruvate into carbon dioxide Electron Transport Chain: inner membrane of mitochondrion; electrons passed to

oxygen

Overview of Glycolysis

 The Embden-Meyerhof (Warburg) Pathway was discovered by Hans Buchner and

Eduard Buchner when sucrose was found rapidly fermented into alcohol by yeast; Essentially all cells carry out glycolysis Enzyme driven Site of glycolysis is in cytosol Ten reactions - same in all cells - but rates differ Two phases: First phase converts glucose to Bishydroxyacetone phosphate and Glyceraldehyde 3-phosphate Second phase produces two pyruvates Products are pyruvate, ATP and NADH

Possible fates for pyruvate

Pyruvic acid: Moves on to the Krebs cycle in an aerobic pathway Is reduced to lactic acid in an anaerobic environment

Glycolysis

Glycolysis: Phases
Phase 1: Sugar activation Two ATP molecules activate glucose into fructose-1,6-diphosphate Phase 2: Sugar cleavage Fructose-1,6-bisphosphate is cleaved into two 3-carbon isomers Bishydroxyacetone phosphate

 Glyceraldehyde 3-phosphate Phase 3: Oxidation and ATP formation The 3-carbon sugars are oxidized (reducing NAD+) Inorganic phosphate groups (Pi) are attached to each oxidized fragment The terminal phosphates are cleaved and captured by ADP to form four ATP molecules. The final products are: Two pyruvic acid molecules Two NADH + H+ molecules (reduced NAD+) A net gain of two ATP molecules

Krebs Cycle: Preparatory Step

Occurs in the mitochondrial matrix and is fueled by pyruvic acid and fatty acids Pyruvic acid is converted to acetyl CoA Decarboxylation Carbon is removed from pyruvic acid Carbon dioxide is released Oxidation Hydrogen atoms are removed from pyruvic acid NAD+ is reduced to NADH + H+ Formation of acetyl CoA the resulting acetic acid is combined with coenzyme A, a sulfur-containing coenzyme, to form acetyl CoA

Krebs Cycle
An eight-step cycle in which each acetic acid is decarboxylated and oxidized, generating: Three molecules of NADH + H+ One molecule of FADH2 Two molecules of CO2 One molecule of ATP For each molecule of glucose entering glycolysis, two molecules of acetyl CoA enter the Krebs cycle

Electron Transport Chain Food (glucose) is oxidized and the released hydrogens: Are transported by coenzymes NADH and FADH2 Enter a chain of proteins bound to metal atoms (cofactors) Combine with molecular oxygen to form water Release energy The energy released is harnessed to attach inorganic phosphate groups (Pi) to ADP, making ATP by oxidative phosphorylation Mechanism of Oxidative Phosphorylation
The hydrogens delivered to the chain are split into protons (H+) and electrons

The protons are pumped across the inner mitochondrial membrane by: NADH dehydrogenase (FMN, Fe-S) Cytochrome b-c1 Cytochrome oxidase (a-a3) The electrons are shuttled from one acceptor to the next Electrons are delivered to oxygen, forming oxygen ions Oxygen ions attract H+ to form water H+ pumped to the intermembrane space: Diffuses back to the matrix via ATP synthase Releases energy to make ATP

Mechanism of Oxidative Phosphorylation

ATP Synthetase

 The enzyme consists of three parts: a rotor, a knob, and a rod Current created by H+ causes the rotor and rod to rotate This rotation activates catalytic sites in the knob where ADP and Pi are combined to make ATP Summary of ATP Production

LACTOSE FERMENTATION Anaerobic pathway

Occurs in reduced supply of oxygen

METABOLISM OF LACTIC ACID Oxidation: to pyruvate by well oxygenated muscle cells which is then directly used to fuel the Krebs cycle, Conversion: to glucose via gluconeogenesis in the liver and release back into the circulation, (Cori cycle). CORIS CYCLE

Glycogenesis and Glycogenolysis

Glycogenesis formation of glycogen when glucose supplies exceed cellular need for ATP synthesis Glycogenolysis breakdown of glycogen in response to low blood glucose Gluconeogenesis The process of forming sugar from noncarbohydrate molecules Takes place mainly in the liver Protects the body, especially the brain, from the damaging effects of hypoglycemia by ensuring ATP synthesis can continue LIPOLYSIS

LIPOGENESIS

PROTEIN METABOLISM

METABOLISM DISORDERS What is a metabolic disease? Inborn errors of metabolism any disease originating in our chemical individuality inborn error : an inherited (i.e. genetic) disorder metabolism : chemical or physical changes undergone by substances in a biological system What is a metabolic disease? Garrods hypothesis A B deficiency substrate excess Classification: Small molecule disease Carbohydrate Protein Lipid Nucleic Acids Organelle disease C (product) D toxic metabolite

Lysosomes Mitochondria Peroxisomes Cytoplasm

G6-PD DEFICIENCY G6PD is one of many enzymes that help the body process carbohydrates and turn them into energy G6PD also protects red blood cells from potentially harmful byproducts that can accumulate when a person takes certain medications or when the body is fighting an infection. Without enough G6PD to protect them, RBCs can be damaged or destroyed. G6PD deficiency is an X linked inherited condition. This deficiency can cause hemolytic anemia, usually after exposure to certain medications, foods, or even infections. Normally don't have any symptoms Symptoms disappear once the cause, or trigger, is removed Rarely leads to chronic anaemia. With right precautions patient can lead healthy life. Pyruvate kinase (PK) deficiency:
This is the next most common red cell enzymopathy after G6PD deficiency, but is

rare. It is inherited in a autosomal recessive pattern and is the commonest cause of the socalled "congenital non-spherocytic haemolytic anaemias" (CNSHA). PK catalyses the conversion of phosphoenolpyruvate to pyruvate with the generation of ATP. Inadequate ATP generation leads to premature red cell death. CLINICAL FEATURES Most patients are anaemic or jaundiced in childhood. Gallstones, splenomegaly, aplastic crises and skeletal deformities due to marrow expansion may occur. Individuals who are most severely affected may die in utero of anemia or may require blood transfusions or splenectomy. TREATMENT Most affected individuals do not require treatment. Treatment can include a blood transfusion or removal of the spleen. Treatment is usually effective in reducing the severity of the symptoms. Glycogen storage disease (Glycogenoses)

 CLINICAL FEATURES Impairs the ability of the liver to produce free glucose from glycogen and from gluconeogenesis Some neonates die at first year of life while others have asymtomatic disease Enlarged liver. Hyperlipidaemia Hypoglycaemia Muscle weakness, myopathy, Exercise intolerance and cramps. Growth failure Heart failure Renal failure Heamolytic anaemia

D o e is rd r Tp 0 ye T p IA ye T p IB ye

A ce T s e ffe t d is u L e iv r L e, k n y iv r id e , in s e te tin L e iv r G cgn ly o e

Ezm ny e s n ae y th s

G c s -6-p o p a s lu o e h s h ta e

G c s -6-p o p a lu o e h s h te tra s o r (T1 n p rte ) CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROMES (CDGS) T p IC ye L e iv r P o p a tra s o r h s h te n p rte Autosome recessive disorders characterised by disorder in glycosylation. Clinical features- hypoglycaemia, vomiting , diarrhea, hepatic fibrosis, retinopathy Tthrombosis. p L e, m s h , h a iv r u c le e rt G c g nd b n h g ly o e e ra c in and recurrent y eIIIA ezm ny e No treatment Tp ye REFERENCES IIIB L e iv r G c g nd b n h g ly o e e ra c in ezm ny e

Wikipaedia T p IV ye L e iv r G c g np o p o la e ly o e h s h ry s Text book of biochemistry by Thomas M. Devlin http://www.unisanet.unisa.edu.au/08366/timages/aametab.gif T p IX ye L e, e th c te , iv r ry ro y s L r o rm f iv -s b n uui http://www.metabolic-database.com/html/lipogenesis_main_page.html e is fo o le k c te liv r a d m s le e n uc http://images.google.co.in/imgres?u o y s p s h ry s in s h imgurl=http://www.nature.com/embor/journal/v2/n4/images/embor440-o p o la ek a e f1.gif&imgrefurl=http://www.nature.com/embor/journal/v2/n4/fig_tab/embor440_f1. html&usg=__GhXW98YZxUiJzSt9OYOceZVZEQo=&h=333&w=600&sz=51&hl=e L e, m s le iv r -s b n o liv r a d m s l u u it f e n u c n&start=1&um=1&itbs=1&tbnid=hZ9e- u c , e th c te , ry ro y s P K VY2xT5JbM:&tbnh=75&tbnw=135&prev=/images%3Fq%3Dlipogenesis%26um %3D1%26hl%3Den%26sa%3DN%26tbs%3Disch:1 le k c te uoy s http://images.google.co.in/imgres? imgurl=http://stevebambas.com/images/05_Lipogenesis.jpg&imgrefurl=http://steveba rmo L e iv r T s /liv r is fo e tis e o f sbn o P u u it f K

mbas.com/AP%2520210%2520Metabolism.htm&usg=__p9_s7c5dbwTYrqoVm8zaO_qir0=&h=604&w=383&sz=19&hl=en&start=17&um=1&itbs=1&tbnid= crBFulPVuH3doM:&tbnh=135&tbnw=86&prev=/images%3Fq%3Dlipogenesis %26um%3D1%26hl%3Den%26sa%3DN%26tbs%3Disch:1 http://en.wikipedia.org/wiki/Glycogen_storage_disease http://www.pathologyportal.org/97th/pdf/companion22h03.pdf http://emedicine.medscape.com/article/125096-overview http://kidshealth.org/parent/general/aches/g6pd.html#